Derivatives of 3,4-dihydroxyphenylaminopropanols



Patented Mar. 21, 1939 UNITED STATES PATENT OFFICE DERIVATIVES OF 3,4-DIHYDROXYPHENYL- AMINOPROPANOLS Max Bockmiihl, Gustav Ehrhart, and Leonhard Stein, Frankfort-on-the-Main, .Germany, assignors to Winthrop Chemical Company, Inc., New York, N. Y., a corporation of New York No Drawing. Application June 27, 1936, Serial No. 87,800. In Germany July 14, 1935 3 Claims. (01. 260572) suction and the alcoholic filtrate is concentrated under reduced pressure. The residue is dissolved in 200 cc. of water and the 3,4-dihydroxyethylaminopropiophenone is precipitated in a crystalline form from the hydrochloric acid solution by means of ammonia. The keto base obtained melts at 169 C. to 170 C. with decomposition. The 3,4-dihydroxyethylaminopropiophenone thus obtained is dissolved in the calculated amount of hydrochloric acid, diluted with water and again C hydrogenated with palladium andv hydrogen. I H After the absorption of the calculated amount H of hydrogen the catalyst is removed by filtering H with suction, the aqueous solution is concentrated "l5 under reduced pressure and the crystalline resiwherein X stands for an aliphatic hydrocarbon due is recrystallized from methanol with addiradical with at least two carbon atoms or for a tion of ether. The 3 4 djhydroxyphenylethyl cycloaliphatic hydrocarbon ra have an aminopropanol hydrochloride melts, after reachon on the heart analogous to that of crystallization, at 211 c. with decomposition.

dihydrOXyphenylmethylaminoethanol, but Sllrgrams of 3 4 dibenzyloxypropiophenone isingly scarcely infect the blood pressureare dissolved in 250 cc. of methylene chloride and Thus there is obtained, for instance, the 3,4- mixed after addition of 30 grams of l i dihydroXyphenylalkylaminopropanol-l bl'O- carbonate drop drop grams of bro- I mina'tmn of 3,4dihydroxypropiophenona prefermine. The liquid obtained after the reaction is ably after D evious benzylation and Substitution filtered, washed with ice water, dried over sodium 25 of the bromine by the alkylamine 011p and sulfate and concentrated in a vacuum. The 3,4- duction Of the alkylamine ketone obtained. dibenzyloxybromopropiophenone remains The following examples serve o illustrate the is dissolved in 100 cc. of alcohol and directly invention, but are not t0 caused to react grams of thereto! amine. The solution is allowed to stand over 30 (1) 04 rams f ,4-di y x p p night and then mixed with such an amount of none are dissolved in 300 cc. of methylene chloride ether t t t benzylpropylamine hydrobromide and mixed, drop by drop, with 48 grams of formed during the reaction precipitates. The bromine. When the brominationis complete the whole is filtered t suction and t filtrate as liquid is concentrated under reduced pressure ahd obtained is shaken with an excess of hydrochloric the residue is mixed CC. Of an 31100110110 of per centtrength the 3A djbenzy1oxy ethylamine sfllution. Of per cent. strength. benzylpropy]aminopropiophenone hydrochloride After a reaction lasting for several hours the being obtained in an oily form in t eparating whole is mixed with ether and the ethylamine funnel. The oily hydrochloride is separated, dis- 4 hydrobromide formed during the reaction is pre- Solved in t, 350 cc" of alcohol and hydrocipitated and filtered with suction. The filtrate genated t palladium and hydrogen w obtained iS then shaken Wil71l500 00. 0f hydrothe absorption of hydrogen is complete, the Chloric c of 10 p r 66m?- Strength. the catalyst is eliminated by filtering with suction dibenzylo yethylaminopropiophen n hydrochloand the alcoholic filtrate is evaporated in a ride being obtained in an oily form in the sepavacuum. The non-crystallizing residue is dis- 45 rating funnele Oil s parated, dissolved in solved in 300 cc. of water and, after decolorizaabout 400 .cc. of alcohol and the alcoholic solution with animal charcoal, the aqueous solution tion is hydrogenated with palladium and hydrois again hydrogenated with palladium and hydrogen. When the absorption of hydrogen is comgen. As soon as the absorption of hydrogen has plete, the catalyst is eliminated by filtering with ceased the catalyst is removed by filtering with 50 suction and the aqueous filtrate is dried under reduced pressure. The crystalline residue is recrystallized from a mixture of methanol and. acetone. The 3,4-dihydroxyphenylpropylaminopropanol hydrochloride decomposes at 210 C.

(3) 25 grams of 3,4-dibenzyloxypropiophenone are dissolved in cc. of methylene chloride and caused to react, drop by drop, with 11.6 grams of bromine. The residue obtained after the distillation of the solvent is transformed in an alcoholic solution with the calculated amount of cyclopentylamine. After one days standing thealcoholic solution is mixed with ether, first washed with water and then shaken with 200 cc. of dilute hydrochloric acid, the 3,4-dibenzyloxycyclopentylamidopropiophenone hydrochloride being obtained in the form of an oil at the bottom of the separating funnel. The feebly yellowish oil is separated, diluted with about300 cc. of alcohol and hydrogenated with palladium and hydrogen.

When the absorption of hydrogen is complete the alcoholic solution is concentrated in a vacuum and the residue is dissolved in water, rendered alkaline with the aid of ammonia and the product which crystallizes is filtered with suction. The 3 ,4 dihydroxycyclopentylaminopropiophenone obtained is dissolved in dilute hydrochloric acid,

cyclohexylamine and subsequently hydrogenating. It melts at 242 C. with decomposition.

We claim: 1. As a new product the compound of the following formula: 5 OHOH.GH.CHa

H H2 H0 N/H o H \(J/ \C-H2 1o .LEONHARD STEIN. 

